Older versions of the BCG vaccine may be better at preventing cases of tuberculosis than more commonly used modern vaccines, say French scientists.
BCG is a vaccine which protects against TB
Genetic changes in strains over the years have rendered newer vaccines less effective, the Proceedings of the National Academy of Sciences report.
The researchers at the Institut Pasteur say clinical trials should be done to retest the older strains.
Modern BCG vaccine strains are used in two-thirds of immunisations worldwide.
The BCG vaccine was originally developed by French scientists in 1908 who managed to make a strain of tuberculosis (TB) less potent by growing it in a glycerin-potato mixture.
This meant when used in a vaccine it would produce an immune response without causing the actual disease.
Once they found it was safe, they began to distribute the vaccine around the world.
At that time, the only way to keep the vaccine strain alive in the laboratory was to continue to grow it in the culture.
Genetic analysis of strains sent to Japan and Russia in about 1925 and 'newer' strains that were sent to be used in Europe between the 1930s and 1960's showed that over time important genes were lost from the vaccine strain.
The researchers said because of this loss newer versions of the vaccine may not produce as strong an immune reaction.
A study in babies published last year found that the early Japan strain prompted a stronger immune reaction than three newer strains that are used in 66% of modern immunisations.
Study leader, Dr Roland Brosch, senior researcher at the Institut said: "The earlier strains have undergone fewer genetic changes.
"The later strains were selected because they had the least side effects but maybe the efficiency has become less and less."
He added that as well as looking whether vaccination programmes should be using the earlier strains, research to try and modify the BCG vaccine to make it more effective may be more successful with the older vaccines.
Professor Paul Fine, from the London School of Hygiene and Tropical Medicine said the BCG story was a very complicated one.
"These vaccines have been used for a long time and various different strains have been used but the results have been all over the place.
"There are a number of different hypotheses as to why this is, but evaluating the effectiveness is not a trivial matter - it takes many years of work."
A spokesperson for the Health Protection Agency said the study identified some potentially important differences between various vaccine strains.
"Indeed, one of the 'early' strains identified in the study is currently being re-evaluated in clinical trials funded by the EU," they said.
"A number of other approaches are being actively investigated to improve the protection provided by the current BCG vaccine strains.
"Clinical trials over the next five to seven years will provide evidence as to which approach will be most successful."